Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD. RESULTS: Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years. CONCLUSIONS: Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years.

Combined pulmonary fibrosis and emphysema in systemic sclerosis: A syndrome associated with heavy morbidity and mortality.

BACKGROUND: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) primarily due to tobacco smoking has been reported in connective tissue disease, but little is known about its characteristics in systemic sclerosis (SSc). METHODS: In this retrospective multi-center case-control study, we identified 36 SSc patients with CPFE, and compared them with 72 SSc controls with interstitial lung disease (ILD) without emphysema. RESULTS: Rate of CPFE in SSc patients with CT scan was 3.6%, and 7.6% among SSc patients with ILD. CPFE-SSc patients were more likely to be male (75 % vs 18%, p < 0.0001), smokers (83 % vs 33%, p < 0.0001), and to have limited cutaneous SSc (53 % vs 24% p < 0.01) than ILD-SSc controls. No specific autoantibody was significantly associated with CPFE. At diagnosis, CPFE-SSc patients had a greater decrease in carbon monoxide diffusing capacity (DLCO 39 ± 13 % vs 51 ± 12% of predicted value, p < 0.0001) when compared to SSc-ILD controls, whereas lung volumes (total lung capacity and forced vital capacity) were similar. During follow-up, CPFE-SSc patients more frequently developed precapillary pulmonary hypertension (PH) (44 % vs 11%, p < 10-4), experienced more frequent unscheduled hospitalizations (50 % vs 25%, p < 0.01), and had decreased survival (p < 0.02 by Kaplan-Meier survival analysis) as compared to ILD-SSc controls. CONCLUSIONS: The CPFE syndrome is a distinct pulmonary manifestation in SSc, with higher morbidity and mortality. Early diagnosis of CPFE by chest CT in SSc patients (especially smokers) may result in earlier smoking cessation, screening for PH, and appropriate management.

Diffuse bronchiectasis and airflow obstruction in granulomatosis with polyangiitis.

Parenchymal lung nodes and diffuse intra-alveolar hemorrhage are the archetypal pulmonary manifestations of Granulomatosis with Polyangiitis (GPA). The occurrence of diffuse bronchiectasis and airflow obstruction during GPA is unusual. We report here 3 patients with GPA who developed diffuse bronchiectasis during follow-up. The airflow obstruction seemed then to evolve independently from the GPA itself and ultimately led to respiratory insufficiency. Bronchiectases promoted the occurrence of opportunistic infections, especially with atypical mycobacteria. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 81-84).

[Mucosa-associated lymphoid tissue-derived (MALT) lymphoma]. / Lymphome de type Mucosa-Associated Lymphoid Tissue, (MALT) pulmonaire, puis gastrique.

Pulmonary Mucosa-Associated Lymphoid Tissue (MALT)-type lymphoma is the most frequent primary pulmonary lymphoma. We report the case of a patient who presented a pulmonary MALT-type lymphoma treated with chloraminophen, with a recurrence 5 years later characterized with pulmonary lesions associated with a gastric location. This observation underlines some anatomical and clinical aspects of pulmonary MALT-type lymphoma, and leads to discuss the evolution of its physiopathological and therapeutic concepts. In particular, the contributions of positron emission tomography and molecular biology allow the analysis of possible multifocal affections of this disease.

[Pulmonary lymphangioleiomyomatosis: From pathogenesis to management]. / Lymphangioléiomyomatose pulmonaire : de la physiopathologie à la prise en charge.

INTRODUCTION: Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease affecting mainly young women. BACKGROUND: The respiratory manifestations are characterized by a progressive cystic destruction of the lung parenchyma. Extrapulmonary involvement includes benign renal tumours called angiomyolipomas and abdominal lymphatic masses called lymphangioleiomyomas. At the pathological level, the cellular proliferation found in LAM is in part due to the presence of mutations in the tumour suppressor genes TSC1 and TSC2 (Tuberous Sclerosis Complex). These mutations lead to the activation of the mTOR pathway, which is currently the main therapeutic target. mTOR inhibitors such as sirolimus or everolimus have shown a beneficial effect on the decline in pulmonary function and a reduction of angiomyolipoma size, but are necessary in only some patients. PERSPECTIVES: LAM cells have migratory properties mediated by the formation of new lymphatic vessels. They are also able to secrete metalloproteases, which enhance their invasiveness. Moreover, the expression of estrogen and progesterone receptors by LAM cells suggests a possible role for sex hormones in the pathogenesis of the disease. CONCLUSION: A better understanding of mTOR-independent mechanisms would allow the development of novel therapeutic approaches.

Severe pulmonary hypertension associated with COPD: hemodynamic improvement with specific therapy.

BACKGROUND: There is no recommendation for treating pulmonary hypertension (PH) when associated with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To evaluate the effect of PH-specific therapy in patients with COPD. METHODS: All successive patients with severe PH [mean pulmonary arterial pressure (mPAP) ≥35 mm Hg] and COPD, who received specific PH medication and who underwent right heart catheterization at baseline and after 3-12 months of treatment, were analyzed from a prospective database. RESULTS: Twenty-six patients were included with a median follow-up of 14 months. Mean forced expiratory volume in 1 s was 57 ± 20% of predicted, and mean forced expiratory volume in 1 s/forced vital capacity was 47 ± 12%. Dyspnea was New York Health Association classification stage (NYHA) II in 15%, NYHA III in 81% and NYHA IV in 4%. First-line treatments were endothelin receptor antagonists in 11 patients, phosphodiesterase-5 inhibitors in 11 patients, calcium blocker in 1 patient, combination therapy in 3 patients including 2 with a prostanoid. After 6 ± 3 months, pulmonary vascular resistance decreased from 8.5 ± 3 to 6.6 ± 2 Wood units (p < 0.001), with significant improvement of cardiac index from 2.44 ± 0.43 to 2.68 ± 0.63 liters × min × m-2 (p = 0.015) and mPAP from 48 ± 9 to 42 ± 10 mm Hg (p = 0.008). There was no significant difference in dyspnea, 6-min walking distance, echocardiographic parameters or N-terminal pro-brain natriuretic peptide levels. There was no significant difference in arterial oxygen saturation after 3-12 months of treatment. CONCLUSIONS: Specific PH medications may improve hemodynamic parameters in COPD patients with severe PH. Appropriate prospective randomized studies are needed to evaluate the potential long-term clinical benefit of treatment.

[Interstitial lung disease-associated with amyopathic dermatomyositis and anti-MDA5 autoantibodies]. / Pneumopathie infiltrante diffuse associée à une dermatomyosite amyopathique avec auto-anticorps anti-MDA5.

INTRODUCTION: Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies is a rare and very recently described clinical entity. CASE REPORT: A 58-year-old woman was admitted with subacute onset of dyspnea (NYHA class IV) associated with cough, oligoarthritis of the wrists, myalgia and intermittent fever. Examination demonstrated skin lesions with heliotrope rash, Gottron's papules, "mechanics hands", and basal inspiratory crackles on lung auscultation. Pulmonary function tests showed a restrictive ventilatory defect, with decreased carbon monoxide diffusion capacity and marked hypoxemia (PaO2 61 mmHg). The chest high-resolution computed tomography appearances were consistent with organizing pneumonia. Bronchoalveolar lavage differential cell count demonstrated 22 % neutrophils. Serum creatine kinase and electromyography were normal ; the serum ferritin level was elevated. Antinuclear antibodies were present and anti-MDA5 autoantibodies were identified. Significant improvement was obtained with systemic corticosteroids, later converted to mycophenolate mofetil as a steroid-sparing agent. CONCLUSION: Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies shares some characteristics with those associated with anti-synthetase antibodies. Muscular involvement may be mild or absent. Early diagnosis and treatment may improve outcome.

Management of idiopathic pulmonary fibrosis in France: a survey of 1244 pulmonologists.

BACKGROUND: The present survey coordinated by the French expert centres for rare pulmonary diseases investigated French pulmonologists' current diagnostic and therapeutic practice for idiopathic pulmonary fibrosis (IPF). METHODS: From December 7, 2011 to February 18, 2012, all French pulmonologists (n = 2608) were contacted. Those who reported following up at least one IPF patient (n = 509) were administered a 26-item questionnaire by phone or e-mail. RESULTS: 509 pulmonologists (41% of responders, 20% of French pulmonologists) were involved in the management of IPF patients. Of those, 36% discussed the cases with radiologists and pathologists. Out of 406 community pulmonologists practicing outside of reference or competence (e.g. expert) centres, 141 (35%) indicated referring patients to those centres. The 2011 international guidelines for IPF were known by 67% of pulmonologists involved in IPF, 84% of whom considered them appropriate for practice. About 58% of patients were diagnosed with mild to moderate IPF as defined by percentage predicted forced vital capacity ≥50% and percentage predicted diffusing capacity of the lung for carbon monoxide ≥35%. Management resulted from multidisciplinary discussion in 36% of the cases. By the end of December 2011, 49% of patients with mild to moderately severe IPF were treated with oral corticosteroids, and 27% received no treatment. CONCLUSIONS: Despite correct awareness of international IPF guidelines, modalities of multidisciplinary discussion and of early diagnosis and management need to be improved through the network of expert centres.

[Alveolar hemorrhage]. / Hémorragie intra-alvéolaire.

Diffuse alveolar hemorrhage (DAH) is defined by the presence of red blood cells originating from the lung capillaries or venules within the alveoli. The diagnosis is established on clinical features, radiological pattern, and especially bronchoalveolar lavage. Diffuse alveolar hemorrhage may have many immune or non-immune causes. Immune causes of DAH include vasculitides, connective tissue diseases, especially systemic lupus erythematosus, and antiglomerular basement membrane antibody disease (Goodpasture's syndrome). Treatment is both supportive and causal, often based on high dose corticosteroids and immunosuppressive therapy (especially intravenous cyclophosphamide). Plasma exchanges are performed in antiglomerular basement membrane antibody disease and systemic lupus erythematosus, and are considered in systemic vasculitis. Non-immune causes of DAH mainly include heart diseases, coagulation disorders, infections, drug toxicities and idiopathic DAH. Treatment of non-immune DAH is that of its cause. Whatever the cause, DAH is an emergency requiring prompt assessment and early treatment.